Monitoring the Early Strength Development of Cement Mortar with Piezoelectric Transducers Based on Eigenfrequency Analysis Method.

Monitoring the early strength formation process of cement is of great importance for structural construction management and safety. In this study, we investigated the relationship between the eigenfrequency and the early strength development of cement mortar. Embedded piezoceramic-based smart aggregates recorded the early strength of cement mortar. An eigenfrequency analysis model demonstrated the relationship between strength and frequency. Experiments were performed by using piezoelectric transducers to monitor the early strength formation process during the testing period. Three types of specimens with different strength grades were tested, and the early strength formation processes were recorded. The experimental results demonstrate that cement mortar strength has a good linear relationship with the resonance frequency, and the average square of the correlation coefficient is greater than 0.98. The results show that structural health monitoring technology is a feasible method of assessing structural safety conditions and has a broad market in the structural construction industry.

Analysis of Population Representation Among Willed Whole-Body Donors to Facilitate the Construction of a Body Donation Program in China: From the Perspective of Medical Students and Anatomists.

The body donation program of Peking Union Medical College was established in May 1999. From May 1999 to December 2017, a total of 5,576 registrants registered and 1,459 donors donated their bodies. Demographic and medical characteristics of the donors were analyzed. The top four causes of death were neoplasms, heart diseases, respiratory diseases, and cerebrovascular diseases. Age at death among donors who died of neoplasms were significantly lower than other causes of death (all p < .05), and the interval between registration and donation among donors who died of neoplasms was significantly shorter than that among donors with other causes (all p < .001). The age of donors when they registered (p < .001) and donated (p < .001) was significantly older than that of general Beijing population. This study may provide a guide for medical colleges or research institutions to establish or enhance their own body donation programs.

SubMito-XGBoost: predicting protein submitochondrial localization by fusing multiple feature information and eXtreme gradient boosting.

MOTIVATION: Mitochondria are an essential organelle in most eukaryotes. They not only play an important role in energy metabolism but also take part in many critical cytopathological processes. Abnormal mitochondria can trigger a series of human diseases, such as Parkinson's disease, multifactor disorder and Type-II diabetes. Protein submitochondrial localization enables the understanding of protein function in studying disease pathogenesis and drug design. RESULTS: We proposed a new method, SubMito-XGBoost, for protein submitochondrial localization prediction. Three steps are included: (i) the g-gap dipeptide composition (g-gap DC), pseudo-amino acid composition (PseAAC), auto-correlation function (ACF) and Bi-gram position-specific scoring matrix (Bi-gram PSSM) are employed to extract protein sequence features, (ii) Synthetic Minority Oversampling Technique (SMOTE) is used to balance samples, and the ReliefF algorithm is applied for feature selection and (iii) the obtained feature vectors are fed into XGBoost to predict protein submitochondrial locations. SubMito-XGBoost has obtained satisfactory prediction results by the leave-one-out-cross-validation (LOOCV) compared with existing methods. The prediction accuracies of the SubMito-XGBoost method on the two training datasets M317 and M983 were 97.7% and 98.9%, which are 2.8-12.5% and 3.8-9.9% higher than other methods, respectively. The prediction accuracy of the independent test set M495 was 94.8%, which is significantly better than the existing studies. The proposed method also achieves satisfactory predictive performance on plant and non-plant protein submitochondrial datasets. SubMito-XGBoost also plays an important role in new drug design for the treatment of related diseases. AVAILABILITY AND IMPLEMENTATION: The source codes and data are publicly available at https://github.com/QUST-AIBBDRC/SubMito-XGBoost/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Etiological serotype and genotype distributions and clinical characteristics of group B streptococcus-inducing invasive disease among infants in South China.

BACKGROUND: Group B streptococcus (GBS)-induced invasive disease is a major cause of illness and death among infants aged under 90 days in China; however, invasive GBS infection remains unknown in China. We aimed to describe the serotype and genotype distributions of early-onset disease (EOD) and late-onset disease (LOD), and to show the clinical correlations among various GBS serotypes and genotypes obtained from infants with invasive GBS infections. METHODS: Between June 1, 2016 and June 1, 2018, 84 GBS strains were collected from patients younger than 90 days at seven Chinese hospitals. Clinical data were retrospectively reviewed. GBS serotyping was conducted and multi-locus sequence typing was performed. RESULTS: Serotypes Ia, Ib, II, III, and V were detected. Serotype III (60.71%) was the most common, followed by Ia (16.67%) and Ib (14.29%). Intrapartum temperature ≥ 37.5 °C, chorioamnionitis, and mortality were noted in 28.57, 42.86, and 28.57% of patients with serotype Ia, respectively, and these rates were higher than those in patients with serotypes Ib and III (P = 0.041, P = 0.031, and P = 0.023, respectively). The incidence of respiratory distress was lower (P = 0.039) while that of purulent meningitis was higher (P = 0.026) in the serotype III group. Eighteen sequence types were detected among isolates, and ST17 [42.86% (36/84)] was the most prevalent. CONCLUSIONS: GBS isolates belonging to serotypes Ia, Ib, and III are common in southern mainland China, and ST17 is highly prevalent. Differences were found in the clinical manifestations of invasive GBS disease induced by serotypes Ia and III.

The top 100 most-cited articles citing human brain banking from 1970 to 2020: a bibliometric analysis.

Many articles involving human brain banks have been published. Bibliometric analysis can determine the history of the development of research and future research trends in a specific field. Three independent researchers retrieved and reviewed articles from the Web of Science database using the following strategy: "TS = (((brain OR cerebral) AND (bank* OR biobank*)) OR brainbank*)." The top 100 most-cited articles were identified and listed in descending order by total citations. Web of Science was used to identify ten recent articles describing bank construction. GeenMedical ( https://www.geenmedical.com/ ) was used to identify ten recent articles from journals with an impact factor (IF) > 20. The top 100 most-cited articles citing human brain banks were published between 1991 and 2017. Fifty-two percent of the articles focused on a specific type of neurodegenerative disease, and 16% discussed the construction and development of human brain banks. Articles using brain tissue had more total and annual citations than those on bank construction. Ten articles with high IFs were published from 2017 to 2019, and they were primarily studies using novel research techniques such RNA sequencing and genome-wide association studies. Most studies were published in journals specializing in neurology or neuroscience such as Movement Disorders (10%), and had been conducted in the United States (52%) by neurologists (62%). The top 100 most-cited articles and recent publications citing human brain banks and their bibliometric characteristics were identified and analyzed, which may serve as a useful reference and pave the way for further research.

Predicting protein-protein interactions by fusing various Chou's pseudo components and using wavelet denoising approach.

Research on protein-protein interactions (PPIs) not only helps to reveal the nature of life activities but also plays a driving role in understanding the mechanisms of disease activity and the development of effective drugs. The rapid development of machine learning provides new opportunities and challenges for understanding the mechanism of PPIs. It plays an important role in the field of proteomics research. In recent years, an increasing number of computational methods for predicting PPIs have been developed. This paper proposes a new method for predicting PPIs based on multi-information fusion. First, the pseudo-amino acid composition (PseAAC), auto-covariance (AC) and encoding based on grouped weight (EBGW) methods are used to extract the features of protein sequences, and the extracted three groups of feature vectors were fused. Secondly, the fused feature vectors are denoised by two-dimensional (2-D) wavelet denoising. Finally, the denoised feature vectors are input to the support vector machine (SVM) classifier to predict the PPIs. The ACC of PPIs of Helicobacter pylori (H. pylori) and Saccharomyces cerevisiae (S. cerevisiae) datasets were 95.97% and 95.55% by 5-fold cross-validation test and compared with other prediction methods. The experimental results show that the proposed multi-information fusion prediction method can effectively improve the prediction performance of PPIs. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/PPIs-WDSVM/.

Prediction of subcellular location of apoptosis proteins by incorporating PsePSSM and DCCA coefficient based on LFDA dimensionality reduction.

BACKGROUND: Apoptosis is associated with some human diseases, including cancer, autoimmune disease, neurodegenerative disease and ischemic damage, etc. Apoptosis proteins subcellular localization information is very important for understanding the mechanism of programmed cell death and the development of drugs. Therefore, the prediction of subcellular localization of apoptosis protein is still a challenging task. RESULTS: In this paper, we propose a novel method for predicting apoptosis protein subcellular localization, called PsePSSM-DCCA-LFDA. Firstly, the protein sequences are extracted by combining pseudo-position specific scoring matrix (PsePSSM) and detrended cross-correlation analysis coefficient (DCCA coefficient), then the extracted feature information is reduced dimensionality by LFDA (local Fisher discriminant analysis). Finally, the optimal feature vectors are input to the SVM classifier to predict subcellular location of the apoptosis proteins. The overall prediction accuracy of 99.7, 99.6 and 100% are achieved respectively on the three benchmark datasets by the most rigorous jackknife test, which is better than other state-of-the-art methods. CONCLUSION: The experimental results indicate that our method can significantly improve the prediction accuracy of subcellular localization of apoptosis proteins, which is quite high to be able to become a promising tool for further proteomics studies. The source code and all datasets are available at https://github.com/QUST-BSBRC/PsePSSM-DCCA-LFDA/ .

Predicting protein submitochondrial locations by incorporating the pseudo-position specific scoring matrix into the general Chou's pseudo-amino acid composition.

Mitochondrion is important organelle of most eukaryotes and play an important role in participating in various life activities of cells. However, some functions of mitochondria can only be achieved in specific submitochondrial location, the study of submitochondrial locations will help to further understand the biological function of protein, which is a hotspot in proteomics research. In this paper, we propose a new method for protein submitochondrial locations prediction. Firstly, the features of protein sequence are extracted by combining Chou's pseudo-amino acid composition (PseAAC) and pseudo-position specific scoring matrix (PsePSSM). Then the extracted feature information is denoised by two-dimensional (2-D) wavelet denoising. Finally, the optimal feature vectors are input to the SVM classifier to predict the protein submitochondrial locations. We obtained the ideal prediction results by jackknife test and compared with other prediction methods. The results indicate that the proposed method is significantly better than the existing research results, which can provide a new method to predict protein locations in other organelles. The source code and all datasets are available at https://github.com/QUST-BSBRC/PseAAC-PsePSSM-WD/ for academic use.

Control of hair follicle cell fate by underlying mesenchyme through a CSL-Wnt5a-FoxN1 regulatory axis.

Epithelial-mesenchymal interactions are key to skin morphogenesis and homeostasis. We report that maintenance of the hair follicle keratinocyte cell fate is defective in mice with mesenchymal deletion of the CSL/RBP-Jkappa gene, the effector of "canonical" Notch signaling. Hair follicle reconstitution assays demonstrate that this can be attributed to an intrinsic defect of dermal papilla cells. Similar consequences on hair follicle differentiation result from deletion of Wnt5a, a specific dermal papilla signature gene that we found to be under direct Notch/CSL control in these cells. Functional rescue experiments establish Wnt5a as an essential downstream mediator of Notch-CSL signaling, impinging on expression in the keratinocyte compartment of FoxN1, a gene with a key hair follicle regulatory function. Thus, Notch/CSL signaling plays a unique function in control of hair follicle differentiation by the underlying mesenchyme, with Wnt5a signaling and FoxN1 as mediators.

Genome-wide significant, replicated and functional risk variants for Alzheimer's disease.

Genome-wide association studies (GWASs) have reported numerous associations between risk variants and Alzheimer's disease (AD). However, these associations do not necessarily indicate a causal relationship. If the risk variants can be demonstrated to be biologically functional, the possibility of a causal relationship would be increased. In this article, we reviewed all of the published GWASs to extract the genome-wide significant (p < 5×10-8) and replicated associations between risk variants and AD or AD-biomarkers. The regulatory effects of these risk variants on the expression of a novel class of non-coding RNAs (piRNAs) and protein-coding RNAs (mRNAs), the alteration of proteins caused by these variants, the associations between AD and these variants in our own sample, the expression of piRNAs, mRNAs and proteins in human brains targeted by these variants, the expression correlations between the risk genes and APOE, the pathways and networks that the risk genes belonged to, and the possible long non-coding RNAs (LncRNAs) that might regulate the risk genes were analyzed, to investigate the potential biological functions of the risk variants and explore the potential mechanisms underlying the SNP-AD associations. We found replicated and significant associations for AD or AD-biomarkers, surprisingly, only at 17 SNPs located in 11 genes/snRNAs/LncRNAs in eight genomic regions. Most of these 17 SNPs enriched some AD-related pathways or networks, and were potentially functional in regulating piRNAs and mRNAs; some SNPs were associated with AD in our sample, and some SNPs altered protein structures. Most of the protein-coding genes regulated by the risk SNPs were expressed in human brain and correlated with APOE expression. We conclude that these variants were most robust risk markers for AD, and their contributions to AD risk was likely to be causal. As expected, APOE and the lipoprotein metabolism pathway possess the highest weight among these contributions.

Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal ß-amyloid deposition in the human brain.

BACKGROUND: Cerebral amyloid angiopathy (CAA) refers to the deposition of ß-amyloid (Aß) peptides in the wall of brain vasculature, commonly involving capillaries and arterioles. Also being considered a part of CAA is the Aß deposition in leptomeninge. The cellular origin of angiopathic Aß and the pathogenic course of CAA remain incompletely understood. METHODS: The present study was aimed to explore the pathogenic course of CAA in the human cerebrum via examination of changes in ß-secretase-1 (BACE1), the obligatory Aß producing enzyme, relative to Aß and other cellular markers, by neuroanatomical and biochemical characterizations with postmortem brain samples and primary cell cultures. RESULTS: Immunoreactivity (IR) for BACE1 was essentially not visible at vasculature in cases without cerebral amyloidosis (control group, n = 15, age = 86.1 ± 10.3 year). In cases with brain amyloid pathology (n = 15, age = 78.7 ± 12.7 year), increased BACE1 IR was identified locally at capillaries, arterioles and along the pia, localizing to endothelia, perivascular dystrophic neurites and meningeal cells, and often coexisting with vascular iron deposition. Double immunofluorescence with densitometric analysis confirmed a site-specific BACE1 elevation at cerebral arterioles in the development of vascular Aß deposition. Levels of BACE1 protein, activity and its immediate product (C99) were elevated in leptomeningeal lysates from cases with CAA relative to controls. The expression of BACE1 and other amyloidogenic proteins in the endothelial and meningeal cells was confirmed in primary cultures prepared from human leptomeningeal and arteriolar biopsies. CONCLUSION: These results suggest that BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Aß deposition, while BACE1 elevation in meningeal cells might contribute Aß to leptomeningeal amyloidosis.

Roles and Mechanisms of Choline Metabolism in Nonalcoholic Fatty Liver Disease and Cancers.

Choline participates in three major metabolic pathways: oxidation, phosphorylation, and acetylation. Through oxidation, choline is converted to betaine and contributes to methyl metabolism and epigenetic regulation. Through phosphorylation, choline participates in phospholipid metabolism, and serves as the precursor of phosphocholine, phosphatidylcholine, glycerophosphocholine, and other essential compounds, thereby modulating lipid metabolism and transport. Through acetylation, choline is transformed into acetylcholine in cholinergic neurons, playing a vital role in neurotransmission. Moreover, gut microbiota can metabolize choline into trimethylamine-N-oxide, and be involved in the pathogenesis of various diseases such as nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease, etc. Since choline metabolism is implicated in the development of NAFLD and diverse cancers, including liver cancer, it may serve as a therapeutic target for these diseases in the future. Currently, there are numerous therapeutic agents targeting choline metabolism to treat NAFLD and cancers, but most of them are ineffective and some even have adverse effects that lead to a series of complications. Therefore, further research and clinical validation are required to obtain safe and efficacious drugs. This review comprehensively summarizes the choline metabolic pathway and its regulatory mechanisms, elucidates the roles and mechanisms of choline metabolism in the aforementioned diseases, and provides a discussion of the current advances and immense potential of this field.

Reduced neurogenesis in human hippocampus with Alzheimer's disease.

Adult hippocampal neurogenesis (AHN), essential for the plasticity of hippocampal structure and function, may be disrupted in Alzheimer's disease (AD). However, the relationship between the changes in AHN and AD-related pathology in humans remains uncertain. By utilizing advanced immunostaining techniques, we could identify multiple biomarkers representing different stages of AHN in postmortem human hippocampal tissue that exhibited various AD-related neuropathological changes. In this study, we observed a significant presence of neurogenic cells in the hippocampus's dentate gyrus (DG) region in 30 individuals, including 14 individuals diagnosed with AD-related neuropathological changes and the remaining 16 individuals without any neurological diseases. Further investigation revealed that patients with AD exhibited pronounced astrogliosis and reduced neurogenesis. Specifically, the number of neuroblasts, immature and early mature granule cells decreased significantly as AD advanced. Although the number of neural stem cells (NSCs) remained unchanged in AD patients compared with mentally healthy individuals, they tended to be more quiescent state regulated by Notch and bone morphogenetic protein (BMP) signaling pathways. These abnormalities were strongly associated with the neuropathological alterations in AD patients. These research findings provide potential insights into the underlying mechanisms that underpin the pathogenesis of AD.

Brain eQTLs of European, African American, and Asian ancestry improve interpretation of schizophrenia GWAS.

Research on brain expression quantitative trait loci (eQTLs) has illuminated the genetic underpinnings of schizophrenia (SCZ). Yet, the majority of these studies have been centered on European populations, leading to a constrained understanding of population diversities and disease risks. To address this gap, we examined genotype and RNA-seq data from African Americans (AA, n=158), Europeans (EUR, n=408), and East Asians (EAS, n=217). When comparing eQTLs between EUR and non-EUR populations, we observed concordant patterns of genetic regulatory effect, particularly in terms of the effect sizes of the eQTLs. However, 343,737 cis-eQTLs (representing ∼17% of all eQTLs pairs) linked to 1,276 genes (about 10% of all eGenes) and 198,769 SNPs (approximately 16% of all eSNPs) were identified only in the non-EUR populations. Over 90% of observed population differences in eQTLs could be traced back to differences in allele frequency. Furthermore, 35% of these eQTLs were notably rare (MAF < 0.05) in the EUR population. Integrating brain eQTLs with SCZ signals from diverse populations, we observed a higher disease heritability enrichment of brain eQTLs in matched populations compared to mismatched ones. Prioritization analysis identified seven new risk genes ( SFXN2 , RP11-282018.3 , CYP17A1 , VPS37B , DENR , FTCDNL1 , and NT5DC2 ), and three potential novel regulatory variants in known risk genes ( CNNM2 , C12orf65 , and MPHOSPH9 ) that were missed in the EUR dataset. Our findings underscore that increasing genetic ancestral diversity is more efficient for power improvement than merely increasing the sample size within single-ancestry eQTLs datasets. Such a strategy will not only improve our understanding of the biological underpinnings of population structures but also pave the way for the identification of novel risk genes in SCZ.

Arteriolosclerosis differs from venular collagenosis in relation to cerebrovascular parenchymal damages: an autopsy-based study.

BACKGROUND AND PURPOSE: Cerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of sclerotic arterioles, the correlation between collagenised venules has not been clarified. Here, we aimed to investigate the associations between microvascular injuries, including arteriolosclerosis and venular collagenosis, and related parenchymal damages in ageing brains, to investigate the underlying correlations. METHODS: We evaluated arteriolosclerosis and venular collagenosis in 7 regions from 27 autopsy cases with no history of stroke or brain tumour. The correlations between the ratio of arteriolosclerosis, venular collagenosis and the severity of cerebrovascular parenchymal damage, including lacunes, microinfarcts, myelin loss, and parenchymal and perivascular haemosiderin deposits, were assessed. RESULTS: Arteriolosclerosis and venular collagenosis became more evident with age. Arteriolosclerosis was associated with lacunes (p=0.004) and brain parenchymal haemosiderin deposits in the superior frontal cortex (p=0.024) but not with leukoaraiosis severity. Venular collagenosis was not associated with the number of lacunes or haemosiderin, while white matter generally became paler with severe venular collagenosis in the periventricular (ß=-0.430, p=0.028) and deep white matter (ß=-0.437, p=0.025). CONCLUSION: Our findings imply an important role for venular lesions in relation to microvessel-related parenchymal damage which is different from that for arteriolosclerosis. Different underlying mechanisms of both cerebral arterioles and venules require further investigation.

Integrative Transcriptomic Analyses of Hippocampal-Entorhinal System Subfields Identify Key Regulators in Alzheimer's Disease.

The hippocampal-entorhinal system supports cognitive function and is selectively vulnerable to Alzheimer's disease (AD). Little is known about global transcriptomic changes in the hippocampal-entorhinal subfields during AD. Herein, large-scale transcriptomic analysis is performed in five hippocampal-entorhinal subfields of postmortem brain tissues (262 unique samples). Differentially expressed genes are assessed across subfields and disease states, and integrated genotype data from an AD genome-wide association study. An integrative gene network analysis of bulk and single-nucleus RNA sequencing (snRNA-Seq) data identifies genes with causative roles in AD progression. Using a system-biology approach, pathology-specific expression patterns for cell types are demonstrated, notably upregulation of the A1-reactive astrocyte signature in the entorhinal cortex (EC) during AD. SnRNA-Seq data show that PSAP signaling is involved in alterations of cell- communications in the EC during AD. Further experiments validate the key role of PSAP in inducing astrogliosis and an A1-like reactive astrocyte phenotype. In summary, this study reveals subfield-, cell type-, and AD pathology-specific changes and demonstrates PSAP as a potential therapeutic target in AD.

A Moisture-Resistant Soft Actuator with Low Driving Voltages for Haptic Stimulations in Virtual Games.

Strong and robust stimulations to human skins with low driving voltages under high moisture working conditions are desirable for wearable haptic feedback applications. Here, a soft actuator based on the "air bubble" electret structure is developed to work in high-moisture environments and produce haptic sensations to human skin with low driving voltages. Experimentally, the water soaking and drying process has been conducted repeatedly for the first time and the 20th time to test the antimoisture ability of the actuator as it recovers its output force up 90 and 65% of the initial value, respectively. The threshold voltages for sensible haptic sensations for the fingertip and palm of volunteers have been characterized as 7 and 10 V, respectively. Furthermore, a demonstration example has been designed and conducted in a virtual boxing game to generate the designated haptic sensations according to the gaming conditions with an accuracy of 98% for more than 100 tests. As such, the design principle, performance characteristic, and demonstration example in this work could inspire various applications with improved reliability for wearable haptic devices.

Focal-type, but not Diffuse-type, Amyloid Beta Plaques are Correlated with Alzheimer's Neuropathology, Cognitive Dysfunction, and Neuroinflammation in the Human Hippocampus.

Amyloid beta (Aß) plaques are one of the hallmarks of Alzheimer's disease (AD). However, currently available anti-amyloid therapies fail to show effectiveness in the treatment of AD in humans. It has been found that there are different types of Aß plaque (diffuse and focal types) in the postmortem human brain. In this study, we aimed to investigate the correlations among different types of Aß plaque and AD-related neuropathological and cognitive changes based on a postmortem human brain bank in China. The results indicated that focal plaques, but not diffuse plaques, significantly increased with age in the human hippocampus. We also found that the number of focal plaques was positively correlated with the severity of AD-related neuropathological changes (measured by the "ABC" scoring system) and cognitive decline (measured by the Everyday Cognitive Insider Questionnaire). Furthermore, most of the focal plaques were co-localized with neuritic plaques (identified by Bielschowsky silver staining) and accompanied by microglial and other inflammatory cells. Our findings suggest the potential of using focal-type but not general Aß plaques as biomarkers for the neuropathological evaluation of AD.

Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans.

Whether adult hippocampal neurogenesis (AHN) persists in adult and aged humans continues to be extensively debated. A major question is whether the markers identified in rodents are reliable enough to reveal new neurons and the neurogenic trajectory in primates. Here, to provide a better understanding of AHN in primates and to reveal more novel markers for distinct cell types, droplet-based single-nucleus RNA sequencing (snRNA-seq) is used to investigate the cellular heterogeneity and molecular characteristics of the hippocampi in macaques across the lifespan and in aged humans. All of the major cell types in the hippocampus and their expression profiles were identified. The dynamics of the neurogenic lineage was revealed and the diversity of astrocytes and microglia was delineated. In the neurogenic lineage, the regulatory continuum from adult neural stem cells (NSCs) to immature and mature granule cells was investigated. A group of primate-specific markers were identified. We validated ETNPPL as a primate-specific NSC marker and verified STMN1 and STMN2 as immature neuron markers in primates. Furthermore, we illustrate a cluster of active astrocytes and microglia exhibiting proinflammatory responses in aged samples. The interaction analysis and the comparative investigation on published datasets and ours imply that astrocytes provide signals inducing the proliferation, quiescence and inflammation of adult NSCs at different stages and that the proinflammatory status of astrocytes probably contributes to the decrease and variability of AHN in adults and elderly individuals.

A Global Multiregional Proteomic Map of the Human Cerebral Cortex.

The Brodmann area (BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice; however, the molecular architecture of BAs remains unknown. The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs. These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns: the motor and sensory cluster, vision cluster, auditory and Broca's area cluster, Wernicke's area cluster, cingulate cortex cluster, and heterogeneous function cluster. We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA. The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex. The brain transcriptome and proteome comparison indicates that they both could reflect the function of cerebral cortex, but show different characteristics. These proteomic data are publicly available at the Human Brain Proteome Atlas (www.brain-omics.com). Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.